Research ArticleClinical Studies

Autoantibody Positivity Is a Risk Factor for Chemotherapy-induced Exacerbation of Interstitial Pneumonia in Lung Cancer

NORIAKI ITO, TAKESHI MASUDA, TAKU NAKASHIMA, SATOSHI NAKAO, KAKUHIRO YAMAGUCHI, SHINJIRO SAKAMOTO, YASUSHI HORIMASU, SHINTARO MIYAMOTO, HIROSHI IWAMOTO, KAZUNORI FUJITAKA, HIRONOBU HAMADA and NOBORU HATTORI
Anticancer Research March 2021, 41 (3) 1497-1506; DOI: https://doi.org/10.21873/anticanres.14908

Abstract

Background: No study has yet investigated the incidence of chemotherapy-induced acute exacerbation of interstitial pneumonia (AE-IP) in patients with autoantibody-positive IP and lung cancer. Herein, we retrospectively compared the incidence of chemotherapy-induced AE-IP in patients with lung cancer between those with autoantibody-positive and -negative IP. Patients and Methods: Between October 2003 and December 2018, patients with lung cancer who received chemotherapy, underwent serological test of antinuclear antibody or rheumatoid factor, and were diagnosed with IP were enrolled. Results: A total of 81 patients were enrolled; autoantibody-positive cases were observed in 23.5%. Autoantibody positivity was an independent risk factor for chemotherapy-induced AE-IP at 6 months after initiation of chemotherapy for lung cancer. The time to onset of AE-IP was significantly shorter in autoantibody-positive patients than in the seronegative patients. Conclusion: Chemotherapy-induced AE-IP developed earlier in patients with autoantibody than in those without. Therefore, the potential development of AE-IP in autoantibody-positive patients warrants monitoring.

Key Words:

Lung cancer is the most lethal type of cancer (1), with 2.4-10.9% of all cases being complicated with interstitial pneumonia (IP) upon lung cancer diagnosis (2). Although the clinical course of IP is usually chronic, certain patients experience acute respiratory deterioration, termed acute exacerbation (AE). The incidence of AE of IP in patients with lung cancer who undergo chemotherapy has been reported to range between 10% and 30% (3, 4). Furthermore, it has been reported that 25-70% of patients with AE-IP do not survive from the onset of AE-IP (5-8). In most of these previous studies, patients with idiopathic IP, which accounts for the majority of cases, were enrolled.

Previous reports have shown that some patients diagnosed with idiopathic IP had autoantibodies, with positive rates for antinuclear antibody (ANA), rheumatoid factor (RF), and anti-cyclic-citrullinated peptide (CCP) at 16.8-56.3%, 6-17.6%, and 1.0-7.3%, respectively (9). To date, patients with IP with autoantibodies but who do not meet the criteria for collagen vascular disease (CVD) are referred to as having IP with autoimmune features (IPAF) (10). The IPAF criteria described a large number of autoantibodies, including ANA, RF, anti-CCP, anti-double-stranded deoxyribonucleic acid (dsDNA), anti-Sjögren’s-syndrome-related antigen A, anti-Sjögren’s-syndrome-related antigen B, anti-ribonucleoprotein, anti-Smith, anti-topoisomerase 1, anti-transfer ribonucleic acid (tRNA), anti-polymyositis-systemic sclerosis, and anti-melanoma differentiation-associated protein 5 antibodies (10). Among these antibodies, ANA (≥1/320) and RF (≥2 ×the upper limit of normal) have been detected in 49.9% and 14.6% of patients with IPAF (11-21). Conversely, the rates of positivity for anti-CCP, anti-dsDNA, anti-Sjögren’s-syndrome-related antigen A and -B for patients with IPAF were reported to be 7.6%, 4.1%, 23.7%, and 3.1%, respectively (11-21). These results indicate that positivity for ANA or RF is higher than that of other antibodies in patients with IPAF. Two previous studies compared the incidence of AE-IP between patients with IPAF and idiopathic IP, showing that the incidence of AE-IP was significantly lower in patients with IPAF than in those with idiopathic IP (16, 17). However, as far as we are aware, there has been no study comparing the incidence of chemotherapy-induced AE-IP between autoantibody-positive and -negative patients with lung cancer.

For patients with advanced lung cancer, immune checkpoint inhibitors (ICI) alone and with platinum doublet chemotherapy is used as standard treatment (22-25). However, pre-existing IP has been reported as a risk factor for the development of ICI-induced AE-IP in patients with non-small-cell lung carcinoma. In addition, the incidence of ICI-induced AE-IP has been reported to be 20-30%, which is higher than that of chemotherapy-induced AE-IP (26-28). Therefore, the frequency of chemotherapy administration to patients with lung cancer with lP as an early line of treatment is higher than that of ICI or ICI with chemotherapy.

Hence, in this study, we retrospectively investigated the incidence of chemotherapy-induced AE-IP in patients with ANA- or RF-positive IP and lung cancer and determined whether autoantibody positivity is a risk factor for the development of AE-IP.

Patients and Methods

Study design and participants. Among patients with advanced lung cancer diagnosed at Hiroshima University Hospital between October 2003 and December 2018, those who had IP and underwent serological tests for ANA or RF, and received chemotherapy using cytotoxic drugs were retrospectively enrolled. Patients who had received definitive radiotherapy or tyrosine kinase inhibitors and were diagnosed with CVD were excluded. We collected patient background and clinical data before the start of chemotherapy, and information on the presence or absence of AE-IP following treatment. This study was approved by the Ethical Committee for Epidemiology of Hiroshima University (no. E-2226). All procedures associated with studies involving human participants were performed in accordance with the ethical standards of the Institutional Research Committee and the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards. Regarding patient consent, the opt-out method was applied in this retrospective study.

Serological evaluation. ANA and RF were investigated before administration of chemotherapy. Positivity for ANA and RF was based on IPAF criteria. For ANA positivity, a titer of at least 1:320 was required (10). RF positivity was defined as a level twice the upper limit of normal or greater (10).

Computed tomographic (CT) evaluation. IP was defined by the existence of bilateral reticulation and consolidation or ground-glass attenuation on CT prior to the initial chemotherapy intervention. The IP patterns were classified into three categories, namely usual IP (UIP), possible UIP, and inconsistent with UIP, based on the statement of American Thoracic Society/European Respiratory Society/Japanese Respiratory Society/Latin American Thoracic Society (29). CT was evaluated by two pulmonologists who were blinded to the patient’s clinical findings, and the final diagnosis was determined in consultation with these pulmonologists.

Definition of AE-IP. Chemotherapy-induced AE-IP was diagnosed when all of the following criteria were met (30): i) Acute exacerbation of dyspnoea within 1 month; ii) new appearance of ground-glass attenuation and infiltration shadows on both sides on CT; iii) no evidence of pulmonary infection (no improvement by antibiotic administration), or overt heart failure; iv) AE-IP developed within 1 month after the latest chemotherapy. AE-IP was evaluated as pneumonitis based on the National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0. (31).

Statistical analysis. A t-test or Wilcoxon rank-sum test was performed to compare the mean values of the two groups. For binary variables, we used the chi-square test. Unless otherwise stated, all results are presented as the median (range). The time to onset of AE-IP was analysed using the Kaplan–Meier method and compared using the log-rank test to examine the significance of differences between groups. Univariate and multivariate analyses using Cox regression model identified risk factors for the development of AE-IP. Previous studies reported that UIP pattern, a low percentage of forced vital capacity, smoking habit, and non-small cell lung cancer are risk factors for AE-IP (32-35). Therefore, we performed multivariate analysis using these factors as covariates. A value of p<0.05 was considered statistically significant. All statistical analyses were performed using JMP® Pro 14.2.0 (SAS Institute Inc., Cary, NC, USA).

Results

Patient characteristics. Data on a total of 1,147 patients with advanced lung cancer were extracted and 182 had IP. Of the 182 patients, no data on either ANA and RF were available for 23. In addition, 78 patients were ineligible for enrolment; finally, 81 patients were enrolled (Figure 1). The comparison of patient characteristics between patients with and without autoantibody is shown in Table I. The proportion of female patients was significantly higher in the autoantibody-positive group than in the -negative group (31.6% vs. 6.5%, p<0.01). The proportion of patients with small-cell lung cancer was significantly lower in the positive group than in the negative group (15.8% vs. 40.3%, p=0.049). Pulmonary function tests showed that the autoantibody-positive group had a significantly lower 1% forced expiratory volume (70.25% vs. 77.3%, p=0.046). No patients had collagenous physical findings.

Figure 1.
Figure 1.

Flowchart of patient enrollment. ANA: Antinuclear antibody; RF: rheumatoid factor.

View this table:
Table I.

Comparison of clinical characteristics between autoantibody-positive and -negative patients.

Chemotherapy regimen. First-line and second-line treatment regimens are presented in Table II. Chemotherapy regimens were classified into three categories according to their risk of chemotherapy-induced AE-IP: High (AE-IP frequency ≥30%), moderate (AE-IP frequency 11-29%), and low (AE-IP frequency ≤10%) (34). There was no significant difference in the proportion of patients in the respective risk groups between the autoantibody-positive and negative groups.

View this table:
Table II.

Comparison of chemotherapy regimens between autoantibody-positive and -negative patients.

Incidence and characteristics of chemotherapy-induced AE-IP. The incidence of AE-IP at 6 months after initiation of chemotherapy was significantly higher in the autoantibody-positive group than in the seronegative group (36.8% vs. 14.5%, p=0.032) (Table III). Conversely, the severity or treatment line of AE-IP was not significantly different between the two groups. Kaplan–Meier analysis showed that the time to onset of AE-IP in the autoantibody-positive group was significantly shorter than in the seronegative group at 6 months (p=0.030). Conversely, this difference was not observed at 1 year (p=0.115) (Figure 2).

View this table:
Table III.

Incidence and characteristics of acute exacerbation of interstitial pneumonia (AE-IP) between autoantibody-positive and - negative patients.

Figure 2.
Figure 2.

Kaplan–Meier analysis of time to onset of acute exacerbation of interstitial pneumonia (AE-IP) according to autoantibody serology. The time to onset in the autoantibody-positive group was significantly shorter than in the seronegative group at 6 months (p=0.030). Conversely, this difference was not observed at 1 year (p=0.115).

Cox proportional hazard analysis for the risk factor of AE-IP. We performed Cox regression analysis to investigate whether patient background factors, including autoantibody positivity, were risk factors for the development of AE-IP at 6 months after chemotherapy initiation (Table IV). Univariate and multivariate analyses showed that autoantibody positivity was a significant factor [hazard ratio=2.845, 95% confidence interval (CI)=1.059-7.647, p=0.038; and 3.624 (1.161-11.309), p=0.026, respectively].

View this table:
Table IV.

Cox analysis of the risk factors of acute exacerbation of interstitial pneumonia.

Kaplan–Meier analysis of time to onset of AE-IP between autoantibody-positive and-negative groups in patients who developed AE-IP. We compared the time to onset of AE-IP between autoantibody-positive and negative groups only in patients who developed AE-IP. Table V lists the characteristics of patients who developed AE-IP in the autoantibody-positive and -negative groups; there were no significant differences in patient characteristics. In addition, chemotherapy regimens at the onset of AE-IP were not significantly different between the groups (Table VI). Kaplan–Meier analysis showed that the time to onset of AE-IP was significantly shorter in the autoantibody-positive group compared to the autoantibody-negative group [median (95% confidence intervaI): at 6 months: 64 (6-155) days vs. not reached (57 days – not reached), log-rank test p=0.035; at 1 year: 64 (6-155) vs. 214 (57-293) days, log-rank test p<0.01] (Figure 3).

View this table:
Table V.

Comparison of patient characteristics between autoantibody-positive and-negative patients who developed acute exacerbation of interstitial pneumonia.

View this table:
Table VI.

Chemotherapy regimens at onset of acute exacerbation of interstitial pneumonia.

Figure 3.
Figure 3.

Kaplan–Meier analysis of time to onset of acute exacerbation of interstitial pneumonia (AE-IP) between autoantibody-positive and - negative patients who developed AE-IP. The time to onset was significantly shorter in the autoantibody-positive group compared to the autoantibody-negative group at 6 months (p=0.035) and 1 year (p<0.01).

Discussion

To the best of our knowledge, this is the first study to investigate the incidence of chemotherapy-induced AE-IP in autoantibody-positive patients with lung cancer. In this study, the incidence of AE-IP at 6 months after initiation of chemotherapy was significantly higher in the autoantibody-positive group than in the seronegative group. Multiple Cox regression analysis showed that autoantibody positivity was an independent risk factor for AE-IP. Furthermore, Kaplan–Meier analysis showed that AE-IP developed earlier in patients with autoantibody than in those without. We showed that the incidence of chemotherapy-induced AE-IP was higher and the onset was earlier in autoantibody-positive patients compared to seronegative patients in this study. Several previous studies have shown that autoantibodies positivity is associated with IP complications in patients with CVD (36-38). Indeed, the RF-positive rate in patients with rheumatoid arthritis was reported to be significantly higher in patients with rheumatoid arthritis-associated interstitial lung disease than in those without (39). In addition, the titers of RF and anti-CCP antibodies were significantly higher in patients with IP and RA than in those without IP (40), and RF positivity has been shown to be a risk factor for IP progression (41). Furthermore, another study showed that patients with dermatomyositis complicated with IP had a higher proportion of antibodies than those without IP (42). These findings support a higher frequency and earlier development of chemotherapy-induced AE-IP in autoantibody-positive patients than in autoantibody-negative patients.

Furthermore, the histopathological features of IP with and without autoantibodies are considered to affect the onset of AE-IP due to chemotherapy. It has been reported that surgical lung biopsy sample in patients with IPAF showed lymphocyte aggregation and lymphocyte infiltration with germinal centres in the lung interstitium (14). Similarly, in autoimmune antibody-positive IP, lymphocyte infiltration would be expected to be higher than in antibody-negative IP. Chemotherapeutic agents directly damage epithelial and endothelial cells in the lungs. After such damage, inflammatory cells migrate from the vasculature into the interstitium, where they release cytokines that induce further inflammation (43). Therefore, chemotherapy-induced AE-IP is likely to occur in patients with lymphocyte-infiltrated IP. This may explain why the autoantibody-positive IP group developed AE-IP more frequently and earlier than the autoantibody-negative group.

In this study, the incidence of the AE-IP at 6 months after initiation of chemotherapy was higher in autoantibody-positive than -negative patients. This is inconsistent with the results of previous studies showing that the IPAF group had a lower frequency of AE-IP compared to those with idiopathic pulmonary fibrosis (16, 17). This discrepancy may be attributable to the fact that immunosuppressive therapy was not administered to most of the autoantibody-positive patients in this study. Steroids and immunosuppressants were administered to several patients with IPAF in a study that showed that the IPAF group had a lower incidence of AE-IP (16). If immunosuppressive therapy had been performed in antibody-positive patients in our study, chemotherapy-induced AE-IP may have been less frequent than in the antibody-negative group.

This study has limitations. Firstly, it was a retrospective study and was conducted at a single facility. Therefore, it is necessary to verify the results through prospective multicentre joint research using a high number of cases. Secondly, AE-IP was not pathologically diagnosed in this study, therefore, the AE-IP findings on CT might reflect non-AE-IP i.e. capillary-leak syndrome arising due to chemotherapy, especially in patients with pre-existing cardiac dysfunction.

In conclusion, we showed that autoantibody positivity was an independent risk factor for developing chemotherapy-induced AE-IP at 6 months after the initiation of chemotherapy for lung cancer. Furthermore, AE-IP developed earlier in patients with autoantibodies than in those without. Therefore, the potential development of chemotherapy-induced AE-IP in autoantibody-positive patients warrants monitoring.

Footnotes

  • Authors’ Contributions

    Noriaki Ito: Conceptualisation, validation, formal analysis, investigation, data curation, writing - original draft, and visualisation. Takeshi Masuda: Conceptualisation, methodology, formal analysis, resources, writing - review and editing. Taku Nakashima: Resources, writing – review and editing, and supervision. Satoshi Nakao: Investigation, resources, writing – review and editing. Kakuhiro Yamaguchi: Resources, writing – review and editing. Shinjiro Sakamoto: resources, writing – review and editing. Yasushi Horimasu: Resources, writing – review and editing. Shintaro Miyamoto: Resources, writing – review and editing. Hiroshi Iwamoto: Resources, writing – review and editing. Kazunori Fujitaka: Resources, writing – review and editing. Hironobu Hamada: Resources, writing – review and editing. Noboru Hattori: Resources, writing – review and editing, supervision, and project administration.

  • Conflicts of Interest

    N. Hattori has received funds from Pfizer, Taiho Pharmaceutical, ONO Pharmaceutical, Chugai Pharmaceutical, Eli Lilly Japan and lecture fees, honoraria from Pfizer, Taiho Pharmaceutical, Chugai Pharmaceutical, and Eli Lilly Japan. K. Fujitaka has received lecture fees, honoraria from Pfizer, Taiho Pharmaceutical, Chugai Pharmaceutical, and Eli Lilly Japan. H. Iwamoto has received lecture fees, honoraria from Taiho Pharmaceutical. S. Miyamoto has received lecture fees, honoraria from Taiho Pharmaceutical. T. Masuda has received lecture fees, honoraria from Taiho Pharmaceutical, Chugai Pharmaceutical, and Eli Lilly Japan. K. Yamaguchi has received lecture fees, honoraria from Pfizer and Chugai Pharmaceutical. The other Authors have no conflicts of interest to declare.

  • Received January 24, 2021.
  • Revision received February 13, 2021.
  • Accepted February 15, 2021.

References

  1. ↵
    1. Siegel RL,
    2. Miller KD and
    3. Jemal A
    : Cancer statistics, 2019. CA Cancer J Clin 69(1): 7-34, 2019. PMID: 30620402. DOI: 10.3322/caac.21551
    OpenUrlCrossRefPubMed
  2. ↵
    1. Naccache JM,
    2. Gibiot Q,
    3. Monnet I,
    4. Antoine M,
    5. Wislez M,
    6. Chouaid C and
    7. Cadranel J
    : Lung cancer and interstitial lung disease: a literature review. J Thorac Dis 10(6): 3829-3844, 2018. PMID: 30069384. DOI: 10.21037/jtd.2018.05.75
    OpenUrlCrossRefPubMed
  3. ↵
    1. Masuda T,
    2. Hirano C,
    3. Horimasu Y,
    4. Nakashima T,
    5. Miyamoto S,
    6. Iwamoto H,
    7. Ohshimo S,
    8. Fujitaka K,
    9. Hamada H and
    10. Hattori N
    : The extent of ground-glass attenuation is a risk factor of chemotherapy-related exacerbation of interstitial lung disease in patients with non-small cell lung cancer. Cancer Chemother Pharmacol 81(1): 131-139, 2018. PMID: 29143072. DOI: 10.1007/s00280-017-3476-5
    OpenUrlCrossRefPubMed
  4. ↵
    1. Ichihara E,
    2. Miyahara N,
    3. Maeda Y and
    4. Kiura K
    : Managing lung cancer with comorbid interstitial pneumonia. Intern Med 59(2): 163-167, 2020. PMID: 31534086. DOI: 10.2169/internalmedicine.3481-19
    OpenUrlCrossRefPubMed
  5. ↵
    1. Minegishi Y,
    2. Takenaka K,
    3. Mizutani H,
    4. Sudoh J,
    5. Noro R,
    6. Okano T,
    7. Azuma A,
    8. Yoshimura A,
    9. Ando M,
    10. Tsuboi E,
    11. Kudoh S and
    12. Gemma A
    : Exacerbation of idiopathic interstitial pneumonias associated with lung cancer therapy. Intern Med 48(9): 665-672, 2009. PMID: 19420811. DOI: 10.2169/internalmedicine.48.1650
    OpenUrlCrossRefPubMed
    1. Isobe K,
    2. Hata Y,
    3. Sakamoto S,
    4. Takai Y,
    5. Shibuya K and
    6. Homma S
    : Clinical characteristics of acute respiratory deterioration in pulmonary fibrosis associated with lung cancer following anti-cancer therapy. Respirology 15(1): 88-92, 2010. PMID: 19947998. DOI: 10.1111/j.1440-1843.2009.01666.x
    OpenUrlCrossRefPubMed
    1. Kato M,
    2. Shukuya T,
    3. Takahashi F,
    4. Mori K,
    5. Suina K,
    6. Asao T,
    7. Kanemaru R,
    8. Honma Y,
    9. Muraki K,
    10. Sugano K,
    11. Shibayama R,
    12. Koyama R,
    13. Shimada N and
    14. Takahashi K
    : Pemetrexed for advanced non-small cell lung cancer patients with interstitial lung disease. BMC Cancer 14: 508, 2014. PMID: 25012241. DOI: 10.1186/1471-2407-14-508
    OpenUrlCrossRefPubMed
  8. ↵
    1. Nakao S,
    2. Yamaguchi K,
    3. Sakamoto S,
    4. Horimasu Y,
    5. Masuda T,
    6. Miyamoto S,
    7. Nakashima T,
    8. Iwamoto H,
    9. Fujitaka K,
    10. Hamada H and
    11. Hattori N
    : Chemotherapy-associated acute exacerbation of interstitial lung disease shortens survival especially in small cell lung cancer. Anticancer Res 39(10): 5725-5731, 2019. PMID: 31570474. DOI: 10.21873/anticanres.13773
    OpenUrlAbstract/FREE Full Text
  9. ↵
    1. Kamiya H and
    2. Panlaqui OM
    : Systematic review and meta-analysis of clinical significance of autoantibodies for idiopathic pulmonary fibrosis. BMJ Open 9(5): e027849, 2019. PMID: 31147365. DOI: 10.1136/bmjopen-2018-027849
    OpenUrlAbstract/FREE Full Text
  10. ↵
    1. Fischer A,
    2. Antoniou KM,
    3. Brown KK,
    4. Cadranel J,
    5. Corte TJ,
    6. du Bois RM,
    7. Lee JS,
    8. Leslie KO,
    9. Lynch DA,
    10. Matteson EL,
    11. Mosca M,
    12. Noth I,
    13. Richeldi L,
    14. Strek ME,
    15. Swigris JJ,
    16. Wells AU,
    17. West SG,
    18. Collard HR,
    19. Cottin V and “ERS/ATS Task Force on Undifferentiated Forms of CTD-ILD”
    : An official European Respiratory Society/American Thoracic Society research statement: interstitial pneumonia with autoimmune features. Eur Respir J 46(4): 976-987, 2015. PMID: 26160873. DOI: 10.1183/13993003.00150-2015
    OpenUrlAbstract/FREE Full Text
  11. ↵
    1. Chartrand S,
    2. Swigris JJ,
    3. Stanchev L,
    4. Lee JS,
    5. Brown KK and
    6. Fischer A
    : Clinical features and natural history of interstitial pneumonia with autoimmune features: A single center experience. Respir Med 119: 150-154, 2016. PMID: 27692137. DOI: 10.1016/j.rmed.2016.09.002
    OpenUrlCrossRefPubMed
    1. Oldham JM,
    2. Adegunsoye A,
    3. Valenzi E,
    4. Lee C,
    5. Witt L,
    6. Chen L,
    7. Husain AN,
    8. Montner S,
    9. Chung JH,
    10. Cottin V,
    11. Fischer A,
    12. Noth I,
    13. Vij R and
    14. Strek ME
    : Characterisation of patients with interstitial pneumonia with autoimmune features. Eur Respir J 47(6): 1767-1775, 2016. PMID: 27103387. DOI: 10.1183/13993003.01565-2015
    OpenUrlAbstract/FREE Full Text
    1. Ahmad K,
    2. Barba T,
    3. Gamondes D,
    4. Ginoux M,
    5. Khouatra C,
    6. Spagnolo P,
    7. Strek M,
    8. Thivolet-Béjui F,
    9. Traclet J and
    10. Cottin V
    : Interstitial pneumonia with autoimmune features: Clinical, radiologic, and histological characteristics and outcome in a series of 57 patients. Respir Med 123: 56-62, 2017. PMID: 28137497. DOI: 10.1016/j.rmed.2016.10.017
    OpenUrlCrossRefPubMed
  14. ↵
    1. Ito Y,
    2. Arita M,
    3. Kumagai S,
    4. Takei R,
    5. Noyama M,
    6. Tokioka F,
    7. Nishimura K,
    8. Koyama T,
    9. Notohara K and
    10. Ishida T
    : Serological and morphological prognostic factors in patients with interstitial pneumonia with autoimmune features. BMC Pulm Med 17(1): 111, 2017. PMID: 28807021. DOI: 10.1186/s12890-017-0453-z
    OpenUrlCrossRefPubMed
    1. Dai J,
    2. Wang L,
    3. Yan X,
    4. Li H,
    5. Zhou K,
    6. He J,
    7. Meng F,
    8. Xu S,
    9. Liang G and
    10. Cai H
    : Clinical features, risk factors, and outcomes of patients with interstitial pneumonia with autoimmune features: a population-based study. Clin Rheumatol 37(8): 2125-2132, 2018. PMID: 29667101. DOI: 10.1007/s10067-018-4111-5
    OpenUrlCrossRefPubMed
  16. ↵
    1. Yoshimura K,
    2. Kono M,
    3. Enomoto Y,
    4. Nishimoto K,
    5. Oyama Y,
    6. Yasui H,
    7. Hozumi H,
    8. Karayama M,
    9. Suzuki Y,
    10. Furuhashi K,
    11. Enomoto N,
    12. Fujisawa T,
    13. Nakamura Y,
    14. Inui N,
    15. Sumikawa H,
    16. Johkoh T,
    17. Colby TV,
    18. Sugimura H and
    19. Suda T
    : Distinctive characteristics and prognostic significance of interstitial pneumonia with autoimmune features in patients with chronic fibrosing interstitial pneumonia. Respir Med 137: 167-175, 2018. PMID: 29605201. DOI: 10.1016/j.rmed.2018.02.024
    OpenUrlCrossRefPubMed
  17. ↵
    1. Lim JU,
    2. Gil BM,
    3. Kang HS,
    4. Oh J,
    5. Kim YH and
    6. Kwon SS
    : Interstitial pneumonia with autoimmune features show better survival and less exacerbations compared to idiopathic pulmonary fibrosis. BMC Pulm Med 19(1): 120, 2019. PMID: 31272428. DOI: 10.1186/s12890-019-0868-9
    OpenUrlCrossRefPubMed
    1. Sambataro G,
    2. Sambataro D,
    3. Torrisi SE,
    4. Vancheri A,
    5. Colaci M,
    6. Pavone M,
    7. Pignataro F,
    8. Del Papa N,
    9. Palmucci S and
    10. Vancheri C
    : Clinical, serological and radiological features of a prospective cohort of Interstitial Pneumonia with Autoimmune Features (IPAF) patients. Respir Med 150: 154-160, 2019. PMID: 30961944. DOI: 10.1016/j.rmed.2019.03.011
    OpenUrlCrossRefPubMed
    1. Hernandez-Gonzalez F,
    2. Prieto-González S,
    3. Brito-Zeron P,
    4. Cuerpo S,
    5. Sanchez M,
    6. Ramirez J,
    7. Agustí C,
    8. Lucena CM,
    9. Paradela M,
    10. Grafia I,
    11. Espinosa G and
    12. Sellares J
    : Impact of a systematic evaluation of connective tissue disease on diagnosis approach in patients with interstitial lung diseases. Medicine (Baltimore) 99(4): e18589, 2020. PMID: 31977850. DOI: 10.1097/MD.0000000000018589
    OpenUrlCrossRefPubMed
    1. Sebastiani M,
    2. Cassone G,
    3. De Pasquale L,
    4. Cerri S,
    5. Della Casa G,
    6. Vacchi C,
    7. Luppi F,
    8. Salvarani C and
    9. Manfredi A
    : Interstitial pneumonia with autoimmune features: A single center prospective follow-up study. Autoimmun Rev 19(2): 102451, 2020. PMID: 31838159. DOI: 10.1016/j.autrev.2019.102451
    OpenUrlCrossRefPubMed
  21. ↵
    1. Tian M,
    2. Huang W,
    3. Ren F,
    4. Luo L,
    5. Zhou J,
    6. Huang D and
    7. Tang L
    : Comparative analysis of connective tissue disease-associated interstitial lung disease and interstitial pneumonia with autoimmune features. Clin Rheumatol 39(2): 575-583, 2020. PMID: 31758424. DOI: 10.1007/s10067-019-04836-3
    OpenUrlCrossRefPubMed
  22. ↵
    1. Reck M,
    2. Rodríguez-Abreu D,
    3. Robinson AG,
    4. Hui R,
    5. Csőszi T,
    6. Fülöp A,
    7. Gottfried M,
    8. Peled N,
    9. Tafreshi A,
    10. Cuffe S,
    11. O’Brien M,
    12. Rao S,
    13. Hotta K,
    14. Leiby MA,
    15. Lubiniecki GM,
    16. Shentu Y,
    17. Rangwala R,
    18. Brahmer JR and KEYNOTE-024 Investigators
    : Pembrolizumab versus Chemotherapy for PD-L1-Positive Non-Small-Cell Lung Cancer. N Engl J Med 375(19): 1823-1833, 2016. PMID: 27718847. DOI: 10.1056/NEJMoa1606774
    OpenUrlCrossRefPubMed
    1. Paz-Ares L,
    2. Luft A,
    3. Vicente D,
    4. Tafreshi A,
    5. Gümüş M,
    6. Mazières J,
    7. Hermes B,
    8. Çay Şenler F,
    9. Csőszi T,
    10. Fülöp A,
    11. Rodríguez-Cid J,
    12. Wilson J,
    13. Sugawara S,
    14. Kato T,
    15. Lee KH,
    16. Cheng Y,
    17. Novello S,
    18. Halmos B,
    19. Li X,
    20. Lubiniecki GM,
    21. Piperdi B,
    22. Kowalski DM and KEYNOTE-407 Investigators
    : Pembrolizumab plus chemotherapy for squamous non-small-cell lung cancer. N Engl J Med 379(21): 2040-2051, 2018. PMID: 30280635. DOI: 10.1056/NEJMoa1810865
    OpenUrlCrossRefPubMed
    1. Hellmann MD,
    2. Paz-Ares L,
    3. Bernabe Caro R,
    4. Zurawski B,
    5. Kim SW,
    6. Carcereny Costa E,
    7. Park K,
    8. Alexandru A,
    9. Lupinacci L,
    10. de la Mora Jimenez E,
    11. Sakai H,
    12. Albert I,
    13. Vergnenegre A,
    14. Peters S,
    15. Syrigos K,
    16. Barlesi F,
    17. Reck M,
    18. Borghaei H,
    19. Brahmer JR,
    20. O’Byrne KJ,
    21. Geese WJ,
    22. Bhagavatheeswaran P,
    23. Rabindran SK,
    24. Kasinathan RS,
    25. Nathan FE and
    26. Ramalingam SS
    : Nivolumab plus ipilimumab in advanced non-small-cell lung cancer. N Engl J Med 381(21): 2020-2031, 2019. PMID: 31562796. DOI: 10.1056/NEJMoa1910231
    OpenUrlCrossRefPubMed
  25. ↵
    1. West H,
    2. McCleod M,
    3. Hussein M,
    4. Morabito A,
    5. Rittmeyer A,
    6. Conter HJ,
    7. Kopp HG,
    8. Daniel D,
    9. McCune S,
    10. Mekhail T,
    11. Zer A,
    12. Reinmuth N,
    13. Sadiq A,
    14. Sandler A,
    15. Lin W,
    16. Ochi Lohmann T,
    17. Archer V,
    18. Wang L,
    19. Kowanetz M and
    20. Cappuzzo F
    : Atezolizumab in combination with carboplatin plus nab-paclitaxel chemotherapy compared with chemotherapy alone as first-line treatment for metastatic non-squamous non-small-cell lung cancer (IMpower130): a multicentre, randomised, open-label, phase 3 trial. Lancet Oncol 20(7): 924-937, 2019. PMID: 31122901. DOI: 10.1016/S1470-2045(19)30167-6
    OpenUrlCrossRefPubMed
  26. ↵
    1. Ikeda S,
    2. Kato T,
    3. Kenmotsu H,
    4. Ogura T,
    5. Iwasawa S,
    6. Sato Y,
    7. Harada T,
    8. Kubota K,
    9. Tokito T,
    10. Okamoto I,
    11. Furuya N,
    12. Yokoyama T,
    13. Hosokawa S,
    14. Iwasawa T,
    15. Yamanaka T and
    16. Okamoto H
    : A Phase 2 Study of Atezolizumab for Pretreated NSCLC With Idiopathic Interstitial Pneumonitis. J Thorac Oncol 15(12): 1935-1942, 2020. PMID: 32858235. DOI: 10.1016/j.jtho.2020.08.018
    OpenUrlCrossRefPubMed
    1. Kanai O,
    2. Kim YH,
    3. Demura Y,
    4. Kanai M,
    5. Ito T,
    6. Fujita K,
    7. Yoshida H,
    8. Akai M,
    9. Mio T and
    10. Hirai T
    : Efficacy and safety of nivolumab in non-small cell lung cancer with preexisting interstitial lung disease. Thorac Cancer 9(7): 847-855, 2018. PMID: 29782069. DOI: 10.1111/1759-7714.12759
    OpenUrlCrossRefPubMed
  28. ↵
    1. Yamaguchi T,
    2. Shimizu J,
    3. Hasegawa T,
    4. Horio Y,
    5. Inaba Y,
    6. Yatabe Y and
    7. Hida T
    : Pre-existing pulmonary fibrosis is a risk factor for anti-PD-1-related pneumonitis in patients with non-small cell lung cancer: A retrospective analysis. Lung Cancer 125: 212-217, 2018. PMID: 30429022. DOI: 10.1016/j.lungcan.2018.10.001
    OpenUrlCrossRefPubMed
  29. ↵
    1. Raghu G,
    2. Collard HR,
    3. Egan JJ,
    4. Martinez FJ,
    5. Behr J,
    6. Brown KK,
    7. Colby TV,
    8. Cordier JF,
    9. Flaherty KR,
    10. Lasky JA,
    11. Lynch DA,
    12. Ryu JH,
    13. Swigris JJ,
    14. Wells AU,
    15. Ancochea J,
    16. Bouros D,
    17. Carvalho C,
    18. Costabel U,
    19. Ebina M,
    20. Hansell DM,
    21. Johkoh T,
    22. Kim DS,
    23. King TE Jr.,
    24. Kondoh Y,
    25. Myers J,
    26. Müller NL,
    27. Nicholson AG,
    28. Richeldi L,
    29. Selman M,
    30. Dudden RF,
    31. Griss BS,
    32. Protzko SL,
    33. Schünemann HJ and ATS/ERS/JRS/ALAT Committee on Idiopathic Pulmonary Fibrosis.
    : An official ATS/ERS/JRS/ALAT statement: idiopathic pulmonary fibrosis: evidence-based guidelines for diagnosis and management. Am J Respir Crit Care Med 183(6): 788-824, 2011. PMID: 21471066. DOI: 10.1164/rccm.2009-040GL
    OpenUrlCrossRefPubMed
  30. ↵
    1. Collard HR,
    2. Ryerson CJ,
    3. Corte TJ,
    4. Jenkins G,
    5. Kondoh Y,
    6. Lederer DJ,
    7. Lee JS,
    8. Maher TM,
    9. Wells AU,
    10. Antoniou KM,
    11. Behr J,
    12. Brown KK,
    13. Cottin V,
    14. Flaherty KR,
    15. Fukuoka J,
    16. Hansell DM,
    17. Johkoh T,
    18. Kaminski N,
    19. Kim DS,
    20. Kolb M,
    21. Lynch DA,
    22. Myers JL,
    23. Raghu G,
    24. Richeldi L,
    25. Taniguchi H and
    26. Martinez FJ
    : Acute Exacerbation of Idiopathic Pulmonary Fibrosis. An International Working Group Report. Am J Respir Crit Care Med 194(3): 265-275, 2016. PMID: 27299520. DOI: 10.1164/rccm.201604-0801CI
    OpenUrlCrossRefPubMed
  31. ↵
    1. U.S. Department of Health and Human Services, National Institutes of Health National Cancer Institute
    : Common terminology criteria for adverse events (CTCAE) version 4.0, 2009. Available at: https://www.eortc.be/services/doc/ctc/CTCAE_4.03_2010-06-14_QuickReference_5x7.pdf [Last accessed on 5th February 2021]
  32. ↵
    1. Kenmotsu H,
    2. Naito T,
    3. Kimura M,
    4. Ono A,
    5. Shukuya T,
    6. Nakamura Y,
    7. Tsuya A,
    8. Kaira K,
    9. Murakami H,
    10. Takahashi T,
    11. Endo M and
    12. Yamamoto N
    : The risk of cytotoxic chemotherapy-related exacerbation of interstitial lung disease with lung cancer. J Thorac Oncol 6(7): 1242-1246, 2011. PMID: 21623239. DOI: 10.1097/JTO.0b013e318216ee6b
    OpenUrlCrossRefPubMed
    1. Enomoto Y,
    2. Inui N,
    3. Kato T,
    4. Baba T,
    5. Karayama M,
    6. Nakamura Y,
    7. Ogura T and
    8. Suda T
    : Low forced vital capacity predicts cytotoxic chemotherapy-associated acute exacerbation of interstitial lung disease in patients with lung cancer. Lung Cancer 96: 63-67, 2016. PMID: 27133752. DOI: 10.1016/j.lungcan.2016.03.017
    OpenUrlCrossRefPubMed
  34. ↵
    1. Isobe K,
    2. Kaburaki K,
    3. Kobayashi H,
    4. Sano G,
    5. Sakamoto S,
    6. Takai Y,
    7. Makino T,
    8. Tochigi N,
    9. Iyoda A and
    10. Homma S
    : New risk scoring system for predicting acute exacerbation of interstitial pneumonia after chemotherapy for lung cancer associated with interstitial pneumonia. Lung Cancer 125: 253-257, 2018. PMID: 30429029. DOI: 10.1016/j.lungcan.2018.10.008
    OpenUrlCrossRefPubMed
  35. ↵
    1. Taya T,
    2. Chiba H,
    3. Yamada G,
    4. Takahashi M,
    5. Ikeda K,
    6. Mori Y,
    7. Otsuka M and
    8. Takahashi H
    : Risk factors for acute exacerbation of idiopathic interstitial pneumonia in patients undergoing lung cancer treatment. Jpn J Clin Oncol 49(12): 1126-1133, 2019. PMID: 31411689. DOI: 10.1093/jjco/hyz115
    OpenUrlCrossRefPubMed
  36. ↵
    1. Papiris SA,
    2. Kagouridis K and
    3. Bouros D
    : Serologic evaluation in idiopathic interstitial pneumonias. Curr Opin Pulm Med 18(5): 433-440, 2012. PMID: 22699420. DOI: 10.1097/MCP.0b013e3283560840
    OpenUrlCrossRefPubMed
    1. Pereira DA,
    2. Kawassaki Ade M and
    3. Baldi BG
    : Interpretation of autoantibody positivity in interstitial lung disease and lung-dominant connective tissue disease. J Bras Pneumol 39(6): 728-741, 2013. PMID: 24473767. DOI: 10.1590/S1806-37132013000600012
    OpenUrlCrossRefPubMed
  38. ↵
    1. Bonella F and
    2. Costabel U
    : Biomarkers in connective tissue disease-associated interstitial lung disease. Semin Respir Crit Care Med 35(2): 181-200, 2014. PMID: 24668534. DOI: 10.1055/s-0034-1371527
    OpenUrlCrossRefPubMed
  39. ↵
    1. Zhang Y,
    2. Li H,
    3. Wu N,
    4. Dong X and
    5. Zheng Y
    : Retrospective study of the clinical characteristics and risk factors of rheumatoid arthritis-associated interstitial lung disease. Clin Rheumatol 36(4): 817-823, 2017. PMID: 28191607. DOI: 10.1007/s10067-017-3561-5
    OpenUrlCrossRefPubMed
  40. ↵
    1. Restrepo JF,
    2. del Rincón I,
    3. Battafarano DF,
    4. Haas RW,
    5. Doria M and
    6. Escalante A
    : Clinical and laboratory factors associated with interstitial lung disease in rheumatoid arthritis. Clin Rheumatol 34(9): 1529-1536, 2015. PMID: 26255186. DOI: 10.1007/s10067-015-3025-8
    OpenUrlCrossRefPubMed
  41. ↵
    1. Li L,
    2. Liu R,
    3. Zhang Y,
    4. Zhou J,
    5. Li Y,
    6. Xu Y,
    7. Gao S and
    8. Zheng Y
    : A retrospective study on the predictive implications of clinical characteristics and therapeutic management in patients with rheumatoid arthritis-associated interstitial lung disease. Clin Rheumatol 39(5): 1457-1470, 2020. PMID: 31858341. DOI: 10.1007/s10067-019-04846-1
    OpenUrlCrossRefPubMed
  42. ↵
    1. Li L,
    2. Wang H,
    3. Wang Q,
    4. Wu C,
    5. Liu C,
    6. Zhang Y,
    7. Cheng L,
    8. Zeng X,
    9. Zhang F and
    10. Li Y
    : Myositis-specific autoantibodies in dermatomyositis/polymyositis with interstitial lung disease. J Neurol Sci 397: 123-128, 2019. PMID: 30616054. DOI: 10.1016/j.jns.2018.12.040
    OpenUrlCrossRefPubMed
  43. ↵
    1. Matsuno O
    : Drug-induced interstitial lung disease: mechanisms and best diagnostic approaches. Respir Res 13: 39, 2012. PMID: 22651223. DOI: 10.1186/1465-9921-13-39
    OpenUrlCrossRefPubMed
Back to top

In this issue

Print
Download PDF
Article Alerts
Email Article
Citation Tools
Reprints and Permissions
Autoantibody Positivity Is a Risk Factor for Chemotherapy-induced Exacerbation of Interstitial Pneumonia in Lung Cancer
NORIAKI ITO, TAKESHI MASUDA, TAKU NAKASHIMA, SATOSHI NAKAO, KAKUHIRO YAMAGUCHI, SHINJIRO SAKAMOTO, YASUSHI HORIMASU, SHINTARO MIYAMOTO, HIROSHI IWAMOTO, KAZUNORI FUJITAKA, HIRONOBU HAMADA, NOBORU HATTORI
Anticancer Research Mar 2021, 41 (3) 1497-1506; DOI: 10.21873/anticanres.14908
Twitter logo Facebook logo Mendeley logo

Jump to section

Keywords